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Biomedical subjects

C Beglinger

Publications and source records attributed to C Beglinger.

105 records · Page 6Linked to original sources

Pancreatic polypeptide release: role of stimulants of exocrine pancreatic secretion in dogs.

There are apparent similarities in the mechanisms of the intestinal phase of exocrine and pancreatic polypeptide (PP) secretion by the pancreas. To characterize this relationship, we measured incremental responses of protein, bicarbonate, and PP to graded doses of intravenous secretin, caerulein, CCK8, CCK33, bethanechol, and intraduodenally perfused HCl, sodium oleate, and L-phenylalanine in dogs with gastric and pancreatic fistulas and compared them with average postprandial values. Secretin did not release PP at any dose studied, whereas intraduodenal HCl increased PP levels slightly at a load maximal for pancreatic secretion. Caerulein produced dose-related increases in PP secretion (maximal, 106% of meal response) but CCK8 and CCK33 had much less effect at doses equivalent for protein secretion. Bethanechol was a weak stimulant for PP only at the largest tolerable dose. L-Phenylalanine and sodium oleate markedly increased protein secretion, but only oleate clearly stimulated PP. Our results suggest a greater quantitative importance of the intestinal phase for exocrine than endocrine (PP) pancreatic secretion.

Animals

The effect of an octapeptide somatostatin analogue (SMS 201-995) and somatostatin-14 (SST-14) on pentagastrin-stimulated gastric acid secretion: a comparative study in man.

Using an open, randomised study design, the efficacy and tolerance of SMS 201-995 (a synthetic octapeptide SST-14 analogue with a plasma half-life of 45 min) was compared with that of SST-14 in inhibiting pentagastrin-stimulated gastric acid secretion. In 10 healthy volunteers gastric acid secretion was stimulated for 3.5 hours by an infusion of 3 microgram kg-1 h-1 pentagastrin. One hour after the start of pentagastrin a 2-hour i.v. infusion of either SST-14 (3.5 microgram kg-1 h-1) or one of 4 dosages of SMS 201-995 (0.14, 0.28, 0.56 or 1.12 microgram kg-1 h-1) was started. SMS 201-995 inhibited acid secretion in a dose-dependent manner. The inhibition achieved with the 0.56 and 1.12 microgram kg-1 h-1 dosages was comparable with that obtained with 3.5 microgram kg-1 h-1 SST-14. SMS 201-995 (1.12 microgram kg-1 h-1) appeared to have a longer duration of action than SST-14. No side effects were recorded under either of the test substances.

Adult

[Endocrinology of exocrine pancreas function].

Recent advances in knowledge of the hormonal control of exocrine pancreatic secretion are discussed in the light of two main mechanisms of action: first, the effect of the main regulatory peptides on the exocrine pancreas, and second, the inhibitory mechanisms which may affect pancreatic secretion. A synthesis of the regulatory principles controlling exocrine pancreatic secretion is attempted.

Amino Acid Sequence

Effect of adding albumin to solutions of somatostatin on inhibiting pentagastrin-stimulated acid secretion in dogs.

In five conscious dogs with chronic gastric fistulas we studied the effect of somatostatin solutions on pentagastrin-stimulated acid secretion. Somatostatin was dissolved in 0.154 M NaCl alone or in the same amount of saline to which dog albumin had been added to give a 0.5% solution. Somatostatin produced a dose-dependent inhibition of pentagastrin-stimulated gastric secretion. However, the inhibition was significantly less when somatostatin was dissolved in saline as compared to saline plus albumin. This study suggests that albumin should be added to somatostatin solutions to preserve biological activity, and it confirms previous reports indicating that, without albumin, basic peptides have a tendency to stick to infusion systems.

Albumins

[Addition of albumin to solutions of cholecystokinin (CCK)--effect on pancreatic secretion, plasma CCK level and release of pancreatic polypeptide (PP)].

Dissolving basic peptides such as insulin, secretin, and somatostatin in albumin-containing solutions increases the biologic potency. As CCK-33 also constitutes a basic peptide, it should have similar qualities. In four conscious dogs with chronic gastric and pancreatic Thomas fistulas, we studied the effect of CCK-33 solutions with and without addition of albumin on pancreatic secretin, plasma PP concentration, CCK-like immunoreactivity in plasma and infusion lines. The response of pancreatic protein output (mg/15 min) to increasing doses of 99% pure CCK-33 (0.5; 1; 2; 4 IDU/kg/h) was significantly higher (p less than 0.05) when CCK was dissolved in 0.154 M NaCl with albumin than in NaCl alone. These results were confirmed by measuring plasma CCK-immunoreactivity by CCK-RIA and CCK-immunoreactivity in samples from tips of infusion lines by gastrin-RIA. CCK evoked PP release at increasing doses of CCK-33, which was significantly (p less than 0.05) higher when CCK was dissolved in an albumin-containing solution. There was a significant (p less than 0.02) correlation between plasma PP concentration and pancreatic protein output. Our study shows addition of albumin to solutions of CCK-33 to cause an increase of CCK-33 activity, probably by preventing adsorption of the peptide to glass and plastic surfaces. This is valid for its effect on pancreatic protein secretion as well as PP release.

Albumins

Comparative effects of synthetic and natural secretin on pancreatic secretion and on secretin, insulin, and glucagon levels in man.

The effect of synthetic secretin (Roche) on exocrine pancreatic secretion and on secretin, insulin, and glucagon levels was determined and compared with that of pure natural porcine secretin (GIH, Karolinska Institutet, Stockholm) in 10 healthy volunteers. The two secretin preparations were found to be equipotent. Equipotency applies to pancreatic secretion and to secretin and insulin plasma levels, whereas the plasma levels of glucagon were not affected by either drug. It is concluded that this synthetic secretin preparation is suitable for clinical and research purposes.

Adult

Effect of adding albumin to solutions of cholecystokinin on pancreatic protein output and pancreatic polypeptide release.

In four conscious dogs with chronic gastric and pancreatic Thomas fistulas we studied the effect of 99% pure cholecystokinin-33 (CCK-33) solutions on pancreatic secretion and PP release. CCK-33 was dissolved in 0.154 M NaCl alone or in the same solution containing 1 g per 100 ml dog albumin. The response of pancreatic protein output to increasing doses of CCK-33 (0.5, 1, 2, 4 IDU/kg per h) was significantly (P less than 0.05) higher when CCK was dissolved in NaCl with albumin than in NaCl alone. These results were confirmed by measuring CCK immunoreactivity in samples from tips of infusion lines by a gastrin radioimmunoassay. Release of pancreatic polypeptide (PP) following increasing doses of CCK-33 was also significantly (P less than 0.05) elevated when CCK was dissolved in an albumin-containing solution. There was a significant (P less than 0.02) correlation between plasma concentrations of PP and pancreatic protein output. This study suggests that albumin should be added to CCK-33 solutions to preserve biological activity. The biological effect of CCK-33 may be substantially underestimated if albumin is omitted.

Animals

[Release of pancreatic polypeptide induced by cholecystokinin in man and dog].

In four healthy volunteers increasing doses of intravenous CCK-33 induced an increase in plasma PP concentration measured by RIA. PP concentration rose from a basal level of 67 +/- 15 pmol/l to 198 +/- 45 pmol/l with 2 IDU/kg/h (p less than 0.05). In four mongrel dogs equipped with Thomas cannulas, the same doses induced a more pronounced rise in plasma PP (p less than 0.01). It is concluded that intravenous CCK-33 induces the release of PP in man and dog in a dose-dependent manner.

Animals

The release of pancreatic polypeptide by exogenous CCK in man and dog.

4 healthy volunteers received commercial 20% pure CCK-33 in 4 consecutive doses of 0.5, 1.0, 2.0, 4.0 IDU/kg/h. blood samples were assayed for pancreatic polypeptide (PP) by radioimmunoassay. Plasma PP concentrations increased stepwise from a basal level of 67 +/- 15 pmol/l to a maximum of 198 +/- 46 pmol/l (p less than 0.05). In 4 mongrel dogs with Thomas cannulas, the same doses of 99% pure CCK-33 were successively infused. Plasma PP concentrations rose stepwise with each dose from 44 +/- 7 to 259 +/- 43 pmol/l (p less than 0.02). This rise significantly correlated with pancreatic protein secretion (p less than 0.01). It is concluded that intravenous CCK-33 induces the release of PP in man and in dog, in a dose-dependent manner.

Animals

The release of pancreatic polypeptide by CCK-octapeptide and some analogues in the dog.

In dogs with gastric and pancreatic Thomas fistulas the effect of different cholecystokinin-like peptides upon pancreatic polypeptide (PP) release was studied in three ways: (a) Plasma PP concentrations were determined by radioimmunoassay in response to 135 pmol/kg/h of the synthetic C-terminal octapeptide of cholecystokinin (CCK-OP) (A), of three of its analogues (B, C, D) where methionine has been replaced by methoxinine, and in response to 45 pmol/kg/h of caerulein. The greatest rise in plasma PP concentration expressed as delta PP was achieved with caerulein (327 +/- 37 pM), when taking into account the threefold smaller dose used, followed by CCK-OP (536 +/- 67 pM) and analogues B (343 +/- 51 pM), C (87 +/- 46 pM), and D (32 +/- 15 pM). The order of potency with respect to stimulation of exocrine pancreatic secretion was the same: E and A precede B, C, and D. delta PP correlated linearly with the pancreatic protein output (r = 0.98, p less than 0.01). (b) CCK-OP was infused in four doses of 35, 70, 135, and 270 pmol/kg/h, and plasma PP concentrations and exocrine pancreatic secretion were monitored. The correlation between pancreatic protein output and delta PP was very close (r = 0.98, p less than 0.01). (c) Atropine sulfate (0.1 mg/kg, i.v.) reduced the PP response to the 135 pmol/kg/h dose of CCK-OP by 61%. We conclude from this that CCK-OP and related peptides do release PP and that their effect on exocrine pancreatic secretion is closely correlated with their PP-releasing capacity. The PP release may therefore be used as an indicator of the CCK-like activity of CCK fragments and analogues. CCK-OP may well represent one of the humoral stimulatory factors contributing to the release of PP, but this action appears to depend on a cholinergic background.

Animals

The release of pancreatic polypeptide by intraduodenal l-phenylalanine in the dog.

In four dogs with chronic gastric and pancreatic fistulas 100 mM L-phenylalanine was delivered to the duodenum at a rate of 25 ml/15 minutes. Pancreatic secretion and plasma pancreatic polypeptide (PP) concentration were monitored. Phenylalanine induced a slight rise in pancreatic volume output and a considerable increase in protein secretion in the pancreatic juice as well as a significant (p less than 0.01) increment of plasma PP over basal levels. Administration of atropine sulfate (0.1 mg/kg i.v.) inhibited the PP release and reduced the pancreatic protein output (p less than 0.05). It is concluded that the release of PP following intraduodenal phenylalanine involves a cholinergic mechanism and may be mediated by an enteropancreatic reflex and/or endogenous CCK peptides.

Animals

[Chemical structure and biological activity of cholecystokizin octapeptides with respect to the stomach and pancreas].

Dose response curves of the octapeptide of cholecystokinin (CCK-8) and 3 of its methoxinine analogues have been established in 4 conscious dogs with respect to gastric and pancreatic secretion. In the analogues the methionine was replaced by methoxinine in position 3 (B) and (D) or 6 (C). Of the 4 tested substances CCK-8 exhibited most activity with regard to pancreatic protein secretion, followed by B, C, and D. Analogue C had the strongest stimulating effect on gastric acid secretion, while its effect on pancreatic secretion was minor. Correlation of chemical structure with biological activity points to the importance of the methionine residue in position 6.

Animals

[Modification of smoking behavior using long-distance methods].

906 persons willing to quit smoking were allocated at random to several groups. The results show that (1) an extract of avena sativa has no effect on quantity smoked; (2) distribution of the various parts of a smoking cessation program over several days was no more effective than distribution at once; (3) stopping at once was more effective than progressive reduction of cigarettes smoked.

Edible Grain

Distinct hemodynamic and gastric effects of human CGRP I and II in man.

The human calcitonin gene-related peptides I and II (or alpha and beta) (CGRP I and II) are encoded by two different genes, but they have 34 of the 37 amino acid residues in common. Human CGRP I more potently stimulated blood flow through the skin and carotid artery (p less than 0.01), and the heart rate (p less than 0.05), and plasma renin activity and aldosterone secretion than human CGRP II (p less than 0.02). Inhibition of pentagastrin-stimulated gastric acid output, on the other hand, was only obtained with CGRP II. The separate effects of human CGRP I and II on the cardiovascular and gastric systems are presumably mediated by different receptors or receptor pathways recognized by the two closely related neuropeptides.

Adult